This application proposes to establish a Center under the NIEHS Environmental Health Sciences Center Grants (P30) program in the School of Public Health, at the University of North Carolina (UNC), Chapel Hill. The focus of this "UNC-CH Center on Environmental Health and Susceptibility" is in the area of environmental epidemiology and toxicology. Three research cores will form the intellectual heart of the Center, organized around the following areas of concentration: Genetic Susceptibility, bringing together laboratory and molecular epidemiologic research on genomic determinants of susceptibility; Developmental Susceptibility, addressing the role of different stages in the life cycle and how these influence susceptibility to exposure, with a particular concentration on exposures received from conception through childhood; and Toxicokinetic Susceptibility, reexamining inter-individual variability in physiologic and metabolic factors that are responsible for the wide ranges in response to an exogenous agent. Four facility cores will provide critical services and will result in cost-efficiency for Center investigators: High Throughput Genotyping, Biostatistics and Epidemiologic Methods, Biomarkers, and Nutrient Assessment. The Administrative Core will have responsibility for coordination of Center activities, strategic planning and evaluation: the Pilot Projects Program; membership decisions; financial matters; leadership and visibility for UNC-CH's environmental health research. The Community Education and Outreach Program will assist the Administrative Core in dissemination and education about Center- related themes on environmental health to professionals, the media, and the public at large, with a focus on the state of North Carolina, and will promote two-way scientist/citizen interactions. This Center is designed to maximize cross-disciplinary integration to promote new research collaborations with exciting scientific potential, understand the mechanistic basis of chemical toxicity, and effectively reduce the burden of environmentally-related disease.